Further Applications of Pentachlorophenyl Active Esters in Lengthening Peptide Chains from C- and N-Terminal Amino Acids Using Dicyclohexylamine C-Protection

Abstract

In order to eliminate the problems associated with the use of alkali during peptide synthesis, a systematic investigation was carried out to lengthen peptide chains by coupling N-protected pentachlorophenyl active esters of amino acids and peptides with amino acids and peptides, C-protected by dicyclohexylamine. There was an appreciable increase in yields when N-protected pentachlorophenyl active esters of amino acids were coupled with di- and tripeptides instead of single amino acid units C-protected by dicyclohexylamine. From this, it was concluded that peptide chains would be lengthened more profitably from C-terminal instead of N-terminal amino acid residues when the synthesis of peptides is carried out, using pentachlorophenyl active esters in combination with dicyclohexylamine C-protection. In addition to affording relatively better yields, this approach would further limit the degree of racemization as the active ester component used would always be a monomer.